To keep youthfulness to the end of life is a common desire among all humankind, however, for a long time, humans could not have been spared from changes in their skin with ageing, such as wrinkles, fine wrinkles, saggings, and spots; there has been considered that the human skin or the skin also becomes senescent as we get older and becomes to show apparent changes such as wrinkles, fine wrinkles, saggings, and spots that are, so to speak, “natural providence” and inevitably unavoidable.
Recently, there has been gradually revealed the cause and function of apparent changes in the skin with ageing, such as wrinkles, fine wrinkles, saggings, and spots, as the progress of researches on the structure and the metabolic mechanism of the skin. As well known, the skin is constructed by the outer thin-layer of epidermis (epithelia) and the deeper thick-layer of dermis (connective tissue), wherein the epidermis as the outermost layer protects living bodies from the external world and prevents the exudation of the internal moisture and nutrients to the outside of human bodies; while, the dermis, as a connective tissue having a structure of multifunctionally/three-dimensionally extended fibroblasts, collagens, elastins, proteoglycans, etc., and plays a role in imparting strength, extensibility, or elasticity to the skin. It is also said that, as the reduction of sebum and moisture levels in the skin with ageing, the keratinous layer in the skin surface becomes susceptive to lose its moisture-retaining ability to easily induce fine wrinkles and rough skin due to dryness, etc.
The epidermis is constituted by “keratinous layer” (horny cell layer), “granulosa layer”, “stratum spinosum”, and “stratum germinativum” that are located in this order from the outer side of the skin, where keratinocytes generated in stratum germinativum sequentially move toward the outer side of the skin and mature into keratinous layer, and finally they are peeled off. In particular, keratinocytes proliferate in stratum germinativum existing in the innermost of the skin, and differentiate therein, and then move toward the upper layer of the skin and finally change into a keratinous layer existing in the outermost of the skin and then they are peeled off. These serial processes of keratinocyte proliferation, movement, differentiation, and peeling off are called turnover, wherein keratinocytes newly regenerate at a constant cycle to keep the homeostasis of the skin, however, it is said that the delaying of the turnover of the skin with ageing results in inducing wrinkles, saggings, and rough skin. The turnover rate of the skin varies depending on the part of the human body, however, it is roughly said to be about 20 days for the skin turnover of healthy teenagers, about 28 days for those in 20s, about 40 days for those in 30s, about 55 days for those in 40s as about two times longer than those in 20s, and about 75 days for those in 50s (see Non-Patent Literature 1).
As described above, since the delaying of turnover rate of the skin with ageing is said to induce wrinkles, saggings, and rough skins, even if such a delayed turnover with ageing could be recovered by any means to some extent, wrinkles, saggings, and rough skins can be effectively improved, though the turnover rate in what we call pre-ageing generations including those with ages at around 30 though around 50, who begin to be anxious about the abovementioned skin deteriorations, would hardly be shortened to the normal skin turnover rate of generations in 20s (see Patent Literature 1). From this point of view, turnover rate can be increased by accelerating at least any one of the serial steps of proliferation, movement, differentiation, and peeling off; however, any actual means for solving it has not yet been provided.
A keratinous layer is composed of numerous concentric layers of corneocytes, wherein a solid membrane composed of various proteins such as involucrin called cornified envelope for protecting subcellular site of corneocytes is present in the outermost layer of corneocytes. Such cornified envelope plays an important role in the barrier function of the skin. It is well known that, upon a reduction of the barrier function, ultraviolet (UV) ray, particularly, UV-A (long-wave) that reaches the dermis will damage collagen, elastin, hyaluronic acid, etc.; and that, when the barrier function of the skin decreases, the skin is dried and decreased in its moisture-retaining ability, the oversecretion of sebum is induced, or the disorder of turnover is induced. The barrier function of the skin decreases with ageing, resulting in inducing wrinkles, fine wrinkles, saggings, and spots in the skin (see Patent Literatures 2 and 3).
The barrier function of the skin means the function of keratinous layer called the second barrier as referred to as the function of sebum membrane called the first barrier, i.e., the function for preventing both the invasion of external substances from the outside to the inside of living bodies and the release of excessive amount of moisture from the inside to the outside of living bodies; and means the function for separating the internal and the external region of living bodies with the structure of cell-cell adhesion called tight junction that exists in granular layer of epidermis adjacent to keratinous layer.
The reduction of fibroblasts and hyaluronic acid in dermis induced by ageing, as well as the cleavage of collagen and the denaturation of elastin, allegedly form wrinkles and lower the elasticity of the skin to induce saggings and rough skins. Since elastin, as fibra with a role of supporting collagen fibra, has a role of giving resiliency and elasticity to the skin (see Non-Patent Literature 2). Also, matrix metalloproteinase-1 for decomposing collagen is known to induce wrinkles (see Non-Patent Literature 3).
Endothelin-1, a substance for accelerating the activation and proliferation of melanocyte, is known as a cause of spots. Further, it is noted that pigmentation in the skin (spots) and skin dullness may be induced as a result of unsmooth evacuation of melanin, evacuated from melanocytes into epidermal cells, from epidermal cells (Non-Patent Literature 4).
Based on these research results and findings, there have been proposed a plurality of external dermal agents for reasonably preventing and/or improving apparent spots in the skin with ageing, such as wrinkles, fine wrinkles, saggings, and spots, i.e., external dermal agents for anti-ageing (see, for example, Patent Literatures 4 to 10); mankind are nearing to realize their desire to keep youthfulness to the end of the chapter step by step. The external dermal agents for anti-ageing proposed so far have been realized as a result of pursuing only a few possibilities from among many possibilities, and now still desired is to provide a novel external dermal agent for anti-ageing from more multiple different angles, including another different mechanism of exerting anti-ageing effect, improved handleability, and feasibility of production.